Dithianes, acylation hydrolysis

There are several procedures available for the preparation of acylsilanes. A general synthesis of acyl silanes is via the dithiane route.Hydrolysis of 2-silyl-l,3-dithianes which leads to acyl silanes can be accomplished with mercury(II) salts. To repress formation of aldehyde by-products, various modifications for the deprotection of silyl dithi-anes have been reported, including the use of HgO-F3B OEt2 or chloramine-T. ... 

Another general approach to acyl(methyldiphenyl)silanes starts from 1,3-dithiane (30), which, on lithiation with n-BuLi and subsequent treatment with methyldiphenylchlorosilane forms 2-methyldiphenylsilyl-1,3-dithiane (31a). This may be alkylated following a second deprotonation to yield the corresponding substituted 1,3-dithianes (31b). Hydrolysis of the thioacetals to afford the corresponding acylsilanes (32) was conducted with... 

The (V-methyldihydrodithiazine 125 has also been used as an effective formyl anion equivalent for reaction with alkyl halides, aldehydes, and ketones (77JOC393). In this case there is exclusive alkylation between the two sulfur atoms, and hydrolysis to give the aldehyde products is considerably easier than for dithianes. However, attempts to achieve a second alkylation at C2 were unsuccessful, thus ruling out the use of this system as an acyl anion equivalent for synthesis of ketones. Despite this limitation, the compound has found some use in synthesis (82TL4995). 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

The most general approach to the synthesis of acyl silanes is based on hydrolysis of 2-silyl-l,3-dithioacetals, first investigated for 1,3-dithiane derivatives by Brook56 and Corey57 in the late 1960s (Scheme 3). Oxathioacetals and protected hemithioacetals have also been used, and some formyl silanes have been isolated by hydrolysis of dioxa-acetals (vide supra). 

Cyanide (one carbon) and acetylene (two carbons) are limited and other acyl anion equivalents are more versatile. Dithians are thioacetals of aldehydes that can be deprotonated between the two sulfur atoms by strong bases such as BuLi. Reaction with a second aldehyde gives 27 and hydrolysis of the thioacetal by acid, usually catalysed by Cu(II) or Hg(II), gives the a-hydroxyketone 4. The disconnection is that shown on diagram 4 and the lithium derivative 26 acts as the acyl anion 2. Unlike previous methods, R1 does not have to be H or Me. 

As with our other acyl dithiane oxide systems, the thioacetal moiety can be readily removed by hydrolysis, in this case without affecting the dihydroisoxazoline ring (Scheme 11). 

Acyl-1,3-dithianes are available by the nucleophilic thioacetalisation of ketones bearing an enolisable methylene group with 1,3-propylene bis(p-tolue-nethiolsulfonate) (mp 73 °C).187 The reaction was first applied in the Woodward-Barton synthesis of Lanosterol188 and has since been adapted to some useful synthetic procedures. For example, reaction of the enamine 94,1 [Scheme 2.94] with 13-propylene bis(/ -toluenethiolsulfonate) afforded the 2-acyl-1.3-dithiane 942 after hydrolysis of the enamine. The ability of the dithiane to sta-... 

Oxidative hydrolysis of 2-aeyl-l -dithiane derivatives. A study of the hydrolysis of 2-acyl-1,3-dithianc derivatives by mercuric chloride (HgCl ) has been published. However, hydrolysis of 2-acyl-l,3-dithianes is slow. In this case use of N-haiosuccini-mide reagents is recommended. Either N-bromo uccinimide or N-chlorosuccinimidc-silver nitrate is suitable for oxidative hydrolysis of 1,3-dithiane derivatives. The N-halosuccinimide reagents are useful for hydrolysis of 2-acyl-1,3-dithianes to 1,2-dicarbonyl compounds. 

Most of the chemistry associated with this series of heterocycles is a consequence of the acetal moiety. For example, all three saturated systems undergo acetal hydrolysis, the dioxanes being the most acid-sensitive. The chemistry of 1,3-dithianes and 1,3-oxathianes is further dominated by the acidity of the C-2 protons, leading to the use of the derived carbanions as acyl anion equivalents, particularly in the case of 1,3-dithiane derivatives. Oxidation at sulfur is also a common process. 

Oxidative hydrolysis of an ethylene dithioketal. Cain and Welling report that the method of Corey and Erickson (4,216) for oxidative hydrolysis of 2-acyl-1,3-dithianes is also useful for unmasking of ethylene dithioketals. Thus treatment of the bisethylene dithioketal (1) with 4 eq. of NBS in 10% aqueous acetone at 0° for 20 min. selectively removes the less hindered ethylene dithioketal group at C to give (2) in 80% yield. Removal of the ethylene dithioketal group at C2 with Raney nickel requires reflux in ethanol and is accompanied by reduction of the carbonyl group. 

Due to the stabilizing effect of two sulfur atoms, 1,3-dithianes are easily lithiated at the a-position on treatment with n-BuLi (see 2-Lithio-l,3-dithiane) The 2-lithio-1,3-dithianes constitute an important class of acyl anion equivalents, permitting electrophilic substitution to occur at the masked carbonyl carbon. Hydrolysis of the 1,3-dithiane functionality into a carbonyl group is effected in the presence of mercury(II) ion (eq 4). ... 

Oxidative hydrolysis of 1,3-dithianes using N-halosuccinimides has been extensively investigated . The yields were consistently high when using N-bromosucdnimide (NBS), usually in acetonitrile. Unlike earlier methods 2-acyl-1,3-dithianes were efficiently hydrolysed to 1,2-dicarbonyl compounds. For example, 1-phenyl-1,2-propanedione was prepared in quantitative yield from the 2-benzoyl-2-methyl-l,3-dithiane (equation 14). Silver salts often aid the reaction, but it has been noted that NBS in the... 

One method that achieves the required umpoiung is using a 1,3-dithiane anion as a synthetic equivalent of the acyl anion (the Henry-Nef strategy using a nitroalkane anion offers an analogous approach, but it will not be discussed here). While the acyl anion is unstable and cannot be prepared, the 1,3-dithiane anion is stable due to the inductive withdrawal of electron density by the two sulfur atoms. The 1,3-dithiane anion can be used as a nucleophile and then converted to a carbonyl by hydrolysis. 

Chiral -amino acyl silanes have been prepared throngh the addition of 2-lithio-2-trimethylsilyl-l,3-dithiane to enantiomaicaUy pure iV-tosylaziridines followed by mercury-mediated thioacetal hydrolysis. ... 

Oxidative hydrolysis of 2-alkyl- and 2-acyl-l,3-dithians by iV-halogeno-succinimides is recommended as a high-yield method of carbonyl regeneration the combination of iV-chlorosuccinimide and silver(i) ion is suitable for reaction with unsaturated 1,3-dithians. In a related oxidative procedure, ketones and aldehydes can be readily regenerated from their ethylene thio- or hemithio-acetals by treatment with aqueous chloramine-T. 

On the other hand, the reactions of 2-lithio-2-trimethylsilyl-l,3-dithiane with esters and thioesters give not the ketene dithioacetals, but the 2-acyl-l,3-dithianes 81 (Scheme 2.50). The possibly formed silyl enol ethers 80 undergo subsequent hydrolysis to give 81 [141],... 

Lithiated dithiane 35 is another example of a formyl anion equivalent. Acylation would provide 36 and thioacetal hydrolysis would provide 29. The thioacetal hydrolysis is the FGT that establishes the equivalency. Acylation of dimsyl anion 37 (from metallation of DMSO) would afford )8-ketosulfoxide 38. Once again an oxidation is needed to establish the desired equivalency. This can be accomplished using a Pummerer rearrangement wherein oxidation occurs at carbon with reduction at sulfur. Hydrolysis of the resulting S,0-acetal would complete the required FGT. 

The a-ethylthiosulfoxides can be converted to the corresponding carbonyl compounds by hydrolysis catalyzed by mercuric ion. In both the dithiane and alkylthiomethylsulfoxide systems, an umpolung is achieved on the basis of the carbanion-stabilizing ability of the sulfur substituents. Scheme 13.2 summarizes some examples of synthetic sequences which employ acyl anion equivalents. 

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